Membership of the Royal College of Surgeons (MRCS) Physiology and Applied Surgical Science Syllabus

Why is creatinine clearance used to estimate GFR, and how does it compare to true GFR?

Creatinine is freely filtered and minimally secreted, so it is a convenient endogenous marker, but tubular secretion causes creatinine clearance to slightly overestimate true GFR.

What proportion of filtered sodium and water is reabsorbed in the proximal convoluted tubule, and how?

About 65--70% of filtered $\ce{Na+}$ and water is reabsorbed isosmotically, driven by the basolateral $\ce{Na+}/\ce{K+}$-ATPase, with co-transport of glucose, amino acids and bicarbonate.

Where does aldosterone act in the nephron and what is its effect?

It acts on principal cells of the late distal tubule and collecting duct, increasing $\ce{Na+}$ reabsorption (via ENaC and $\ce{Na+}/\ce{K+}$-ATPase) and $\ce{K+}$ and $\ce{H+}$ excretion.

Outline the renin-angiotensin-aldosterone system (RAAS) cascade.

Renin (from juxtaglomerular cells) converts angiotensinogen to angiotensin I; ACE (lung) converts it to angiotensin II, a potent vasoconstrictor that stimulates aldosterone release, ADH, thirst, and proximal $\ce{Na+}$ reabsorption.

Give the approximate distribution of total body water across compartments.

Total body water $\approx 60\%$ of body weight: intracellular fluid $\approx 40\%$ and extracellular fluid $\approx 20\%$, with ECF split into interstitial ($\approx 15\%$) and plasma ($\approx 5\%$).

State the '60-40-20' rule for body fluid compartments in a 70 kg adult.

Total body water $\approx 60\%$ of weight ($\approx 42\ \text{L}$); intracellular $\approx 40\%$ ($\approx 28\ \text{L}$); extracellular $\approx 20\%$ ($\approx 14\ \text{L}$).

Write the Starling equation governing transcapillary fluid movement.

$J_v = K_f\,[(P_c - P_i) - \sigma(\pi_c - \pi_i)]$, where $P$ are hydrostatic and $\pi$ are oncotic pressures, $K_f$ is the filtration coefficient and $\sigma$ the reflection coefficient.

Compare the major electrolyte compositions of intracellular versus extracellular fluid.

ECF: high $\ce{Na+}$ ($\approx 140\ \text{mmol/L}$), high $\ce{Cl-}$, low $\ce{K+}$ ($\approx 4$). ICF: high $\ce{K+}$ ($\approx 150$), high phosphate/protein, low $\ce{Na+}$ ($\approx 10$).

What are the characteristic ECG changes of hyperkalaemia in progression?

Tall, peaked T waves, then flattened/absent P waves and prolonged PR, widened QRS, and finally a sine-wave pattern progressing to ventricular fibrillation or asystole.

What is the emergency management priority for severe hyperkalaemia, and why?

Intravenous calcium gluconate (or chloride) first to stabilise the cardiac myocyte membrane; then insulin with dextrose and salbutamol to shift $\ce{K+}$ intracellularly, and measures to remove $\ce{K+}$ from the body.

What is the danger of correcting chronic hyponatraemia too rapidly?

Osmotic demyelination syndrome (central pontine myelinolysis); sodium should generally be corrected by no more than about $8\text{--}10\ \text{mmol/L}$ per 24 hours.

Give the RIFLE/KDIGO basis for defining acute kidney injury (AKI).

AKI is defined by a rise in serum creatinine ($\geq 26.5\ \mu\text{mol/L}$ within 48 h, or $\geq 1.5\times$ baseline within 7 days) and/or urine output $< 0.5\ \text{mL/kg/h}$ for $\geq 6$ hours.

Classify the causes of AKI in the surgical patient.

Pre-renal (hypovolaemia/hypoperfusion, e.g. haemorrhage, sepsis), intrinsic renal (acute tubular necrosis, nephrotoxins, contrast), and post-renal (obstruction, e.g. ureteric injury, blocked catheter).

How do urinary indices help distinguish pre-renal AKI from acute tubular necrosis?

Pre-renal: concentrated urine (osmolality $>500$), low urine $\ce{Na+}$ ($<20$), fractional excretion of sodium $FE_{Na} <1\%$. ATN: $FE_{Na} >2\%$, urine $\ce{Na+} >40$, isosthenuric urine. $FE_{Na} = \frac{U_{Na} \times P_{Cr}}{P_{Na} \times U_{Cr}} \times 100\%$.

Which pancreatic islet cells secrete insulin, glucagon and somatostatin?

Beta cells secrete insulin, alpha cells secrete glucagon, and delta cells secrete somatostatin (PP cells secrete pancreatic polypeptide).

What are the principal metabolic actions of insulin?

It lowers blood glucose by promoting glucose uptake (via GLUT4 in muscle/fat), glycogenesis, lipogenesis and protein synthesis, while inhibiting gluconeogenesis, glycogenolysis and lipolysis.

List the counter-regulatory (hyperglycaemic) hormones.

Glucagon, cortisol, growth hormone, and the catecholamines adrenaline/noradrenaline.

Describe the zones of the adrenal cortex and their principal secretions.

Zona glomerulosa secretes mineralocorticoids (aldosterone), zona fasciculata secretes glucocorticoids (cortisol), and zona reticularis secretes androgens; the medulla secretes catecholamines.

What is the hypothalamic-pituitary-adrenal feedback axis for cortisol?

Hypothalamic CRH stimulates pituitary ACTH, which stimulates adrenal cortisol secretion; cortisol exerts negative feedback on both the hypothalamus and pituitary.

Which hormones are released from the posterior pituitary, and what are their roles?

Antidiuretic hormone (vasopressin/ADH), which promotes water reabsorption in the collecting duct, and oxytocin, which causes uterine contraction and milk ejection. These are synthesised in the hypothalamus.

How do thyroid hormones $T_3$ and $T_4$ differ in potency and origin?

$T_4$ (thyroxine) is the main secreted form but is a prohormone; $T_3$ (triiodothyronine) is several times more potent and is largely produced by peripheral deiodination of $T_4$.

What are the three main hormones regulating calcium, and their net effects on serum calcium?

Parathyroid hormone (PTH) raises serum calcium (bone resorption, renal $\ce{Ca}$ reabsorption, activates vitamin D); calcitriol (active vitamin D) raises it (gut absorption); calcitonin lowers it.

Through what mechanisms does PTH raise serum calcium?

It stimulates osteoclastic bone resorption, increases renal distal tubular calcium reabsorption (and phosphate excretion), and activates renal $1\alpha$-hydroxylase to produce active vitamin D, increasing gut calcium absorption.

Describe the ebb and flow phases of the metabolic response to surgery/trauma.

The ebb phase (first ~24--48 h) features hypovolaemia, reduced metabolic rate and cardiac output; the flow (catabolic) phase shows increased metabolic rate, catabolism, negative nitrogen balance, hyperglycaemia and a later anabolic recovery phase.

What hormonal and metabolic changes characterise the catabolic surgical stress response?

Increased cortisol, catecholamines, glucagon, ADH and aldosterone; insulin resistance with hyperglycaemia; protein breakdown with negative nitrogen balance; lipolysis; and sodium/water retention.

Outline the intrinsic and extrinsic coagulation pathways and where they converge.

Extrinsic pathway: tissue factor + factor VII (measured by PT). Intrinsic pathway: factors XII, XI, IX, VIII (measured by APTT). Both converge on the common pathway activating factor X, then prothrombin to thrombin, and fibrinogen to fibrin.

Which clotting factors are vitamin K-dependent?

Factors II, VII, IX and X, plus the anticoagulant proteins C and S.

What is the basis of the ABO blood group system and which is the universal donor?

ABO groups are defined by A and B surface antigens with naturally occurring IgM antibodies against absent antigens. Group O (no A/B antigens) red cells are the universal donor; group AB is the universal recipient.

Why does Rhesus D status matter in transfusion and pregnancy?

RhD-negative individuals can form anti-D IgG antibodies after exposure to RhD-positive blood, causing haemolytic transfusion reactions and, in pregnancy, haemolytic disease of the newborn; hence RhD-negative recipients should receive RhD-negative blood.

Contrast innate and adaptive immunity.

Innate immunity is rapid, non-specific, has no memory (e.g. neutrophils, macrophages, complement, barriers); adaptive immunity is slower, antigen-specific, generates immunological memory, and is mediated by T and B lymphocytes.

What are the four types of graft based on donor-recipient relationship?

Autograft (self to self), isograft (genetically identical, e.g. identical twin), allograft (same species, different genotype), and xenograft (different species).

Classify transplant rejection by timing and mechanism.

Hyperacute (minutes--hours, preformed antibodies), acute (days--weeks, T-cell mediated and/or antibody-mediated), and chronic (months--years, fibrosis and vascular changes).

Describe the structure of the cell membrane (fluid mosaic model).

A phospholipid bilayer with hydrophilic heads outward and hydrophobic tails inward, interspersed with cholesterol, and integral/peripheral proteins, glycoproteins and glycolipids that provide transport, signalling and recognition functions.

Contrast primary and secondary active transport with an example of each.

Primary active transport directly uses ATP (e.g. $\ce{Na+}/\ce{K+}$-ATPase pumping $3\ \ce{Na+}$ out for $2\ \ce{K+}$ in). Secondary active transport uses an ion gradient set up by primary transport (e.g. $\ce{Na+}$-glucose co-transport, SGLT).

What is the typical resting membrane potential of a neuron, and what mainly sets it?

About $-70\ \text{mV}$, set principally by the high resting permeability to $\ce{K+}$ (approaching the $\ce{K+}$ equilibrium potential) maintained by the $\ce{Na+}/\ce{K+}$-ATPase.

Give the Nernst equation for the equilibrium potential of an ion.

$E_{ion} = \frac{RT}{zF}\ln\frac{[\text{ion}]_{out}}{[\text{ion}]_{in}}$, approximately $E_{ion} = \frac{61}{z}\log_{10}\frac{[\text{ion}]_{out}}{[\text{ion}]_{in}}\ \text{mV}$ at $37^{\circ}\text{C}$.

Outline the ionic basis of the neuronal action potential.

Depolarisation to threshold opens voltage-gated $\ce{Na+}$ channels (rapid upstroke); these inactivate while voltage-gated $\ce{K+}$ channels open, causing repolarisation and a brief hyperpolarisation, before the resting potential is restored.

Describe the steps of skeletal muscle excitation-contraction coupling.

Action potential travels down the T-tubule, triggering $\ce{Ca^2+}$ release from the sarcoplasmic reticulum; $\ce{Ca^2+}$ binds troponin C, moving tropomyosin to expose actin binding sites, enabling myosin cross-bridge cycling (sliding filament) powered by ATP.

Name the four main gastrointestinal hormones and their key actions.

Gastrin (stimulates gastric acid secretion), secretin (stimulates pancreatic/biliary bicarbonate), cholecystokinin (CCK; gallbladder contraction and pancreatic enzyme secretion), and gastric inhibitory peptide/GIP (incretin, stimulates insulin).

What stimulates and inhibits gastric acid secretion by parietal cells?

Stimulated by gastrin, histamine (via $H_2$ receptors) and acetylcholine (vagal); the $\ce{H+}/\ce{K+}$-ATPase proton pump is the final step. Inhibited by somatostatin, secretin, and low luminal pH (negative feedback).

How is core body temperature regulated, and what is the controlling centre?

The hypothalamus acts as the thermostat; heat loss is via radiation, conduction, convection and evaporation. Cold triggers vasoconstriction, shivering and thyroid/catecholamine-driven thermogenesis; heat triggers vasodilatation and sweating.

Classify the types of shock by underlying mechanism.

Hypovolaemic (fluid/blood loss), cardiogenic (pump failure), obstructive (e.g. tamponade, tension pneumothorax, PE), and distributive (septic, anaphylactic, neurogenic — loss of vascular tone).

Contrast the haemodynamic profile of septic (distributive) shock with hypovolaemic shock.

Septic shock: low systemic vascular resistance, high/normal cardiac output, warm peripheries early. Hypovolaemic shock: high SVR, low cardiac output, low preload, cold/clammy peripheries with compensatory tachycardia.

What are the four classes of haemorrhagic shock by blood loss volume (ATLS)?

Class I: $<15\%$ ($<750\ \text{mL}$), minimal signs. Class II: $15\text{--}30\%$, tachycardia, narrowed pulse pressure. Class III: $30\text{--}40\%$, hypotension, altered mental state. Class IV: $>40\%$, life-threatening, marked hypotension and oliguria.